Neuroblastoma(NB)is one of the most common malignant tumors in children,with variable clinical behaviors and a 15%death rate of all malignancies in childhood.However,genetic susceptibility to sporadic NB in Han Chines...Neuroblastoma(NB)is one of the most common malignant tumors in children,with variable clinical behaviors and a 15%death rate of all malignancies in childhood.However,genetic susceptibility to sporadic NB in Han Chinese patients is largely unknown.To identify genetic risk factors for NB,we performed an association study on 357 NB patients and 738 control subjects among Han Chinese children.We focused on DEAD box 1(DDX1),a putative RNA helicase,which is involved in NB carcinogenesis.The potential association of DDX1 polymorphisms with NB has not been discovered.Our results demonstrate that rs72780850(NM_004939.2:c.-1555 T>C)located in the DDX1 promoter region is significantly associated with higher expression of DDX1 transcript and increased NB risk(odds ratio=1.64,95%confidence interval=1.03%–2.60%,P=0.004),especially in aggressive NB compared with ganglioneuroma and ganglioneuroblastoma in a dominant model(TC+CC vs.TT).Furthermore,the MYC-associated protein X(MAX)transcription factor showed stronger binding affinity to the DDX1 rs72780850 CC allele compared with the TT allele,explaining the molecular mechanism of the increased NB risk caused by the rs72780850 polymorphism.Our results highlight the involvement of regulatory genetic variants of DDX1 in NB.展开更多
RNA helicases of the DEAD-box and related families are involved in various cellular processes including DNA replication,DNA repair,and RNA processing.However,the function of DEAD-box proteins in aquaculture species is...RNA helicases of the DEAD-box and related families are involved in various cellular processes including DNA replication,DNA repair,and RNA processing.However,the function of DEAD-box proteins in aquaculture species is poorly understood at molecular level.We obtained the full-length cDNA sequences of two genes encoding helicase-related proteins,Fc-vasa and Fc-PL10a,from the testes of Chinese shrimp,Fenneropenaeus chinensis.The two predicted amino acid sequences contain all the conserved motifs characterized by the DEAD-box family and several RGG repeats in the N-terminal regions.Homology and phylogenetic analyses indicate that they belong to the vasa and PL10 subfamilies.The three-dimensional structures of the two proteins were predicted with a homology modeling approach.Both core proteins consist of two tandem RecA-like domains similar to those of the DEAD-box RNA helicase.Using reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR we found that Fc-vasa was expressed specifically in the adult gonads.Transcription decreased in the ovary but increased in the testis during gonadal development.Fc-PL10a expression was widely distributed in the tissues we examined.Using in situ hybridization,we demonstrated that the Fc-vasa transcript is localized to the cytoplasm of the spermatogonia and oocytes.Thus,our results suggest that Fc-vasa plays an important role in germ-line development,and has utility as a germ cell lineage marker which will help to generate new insight into the origin and differentiation of germ cells as well as the regulation of reproduction in F.chinensis.展开更多
The current therapeutic regimen to combat chronic hepatitis C is not optimal due to substantial side effects and the failure of a significant proportion of patients to achieve a sustained virological response.Recently...The current therapeutic regimen to combat chronic hepatitis C is not optimal due to substantial side effects and the failure of a significant proportion of patients to achieve a sustained virological response.Recently developed direct-acting antivirals targeting hepatitis C virus(HCV)enzymes reportedly increase the virologic response to therapy but may lead to a selection of drug-resistant variants.Besides directacting antivirals,another promising class of HCV drugs in development include host targeting agents that are responsible for interfering with the host factors crucia for the viral life cycle.A family of host proteins known as DEAD-box RNA helicases,characterized by nine conserved motifs,is known to play an important role in RNA metabolism.Several members of this family such as DDX3,DDX5 and DDX6 have been shown to play a role in HCV replication and this review will summarize our current knowledge on their interaction with HCV.As chronic hepatitis C is one of the leading causes of hepatocellular carcinoma,the involvement of DEADbox RNA helicases in the development of HCC will also be highlighted.Continuing research on the interaction of host DEAD-box proteins with HCV and the contribution to viral replication and pathogenesis could be the panacea for the development of novel therapeutics against HCV.展开更多
基金supported by the National Natural Science Foundation of China(81472369 and 81502144)Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education(KZ201810025034)+2 种基金Clinical Application Research Funds of Capital Beijing(Z171100001017051)Beihang University&Capital Medical University Advanced Innovation Center for Big Data-Based Precision Medicine Plan(BHME-201804 and BHME201904)The Special Fund of the Pediatric Medical Coordinated Development Center of Beijing Hospitals Authority(XTCX201806)。
文摘Neuroblastoma(NB)is one of the most common malignant tumors in children,with variable clinical behaviors and a 15%death rate of all malignancies in childhood.However,genetic susceptibility to sporadic NB in Han Chinese patients is largely unknown.To identify genetic risk factors for NB,we performed an association study on 357 NB patients and 738 control subjects among Han Chinese children.We focused on DEAD box 1(DDX1),a putative RNA helicase,which is involved in NB carcinogenesis.The potential association of DDX1 polymorphisms with NB has not been discovered.Our results demonstrate that rs72780850(NM_004939.2:c.-1555 T>C)located in the DDX1 promoter region is significantly associated with higher expression of DDX1 transcript and increased NB risk(odds ratio=1.64,95%confidence interval=1.03%–2.60%,P=0.004),especially in aggressive NB compared with ganglioneuroma and ganglioneuroblastoma in a dominant model(TC+CC vs.TT).Furthermore,the MYC-associated protein X(MAX)transcription factor showed stronger binding affinity to the DDX1 rs72780850 CC allele compared with the TT allele,explaining the molecular mechanism of the increased NB risk caused by the rs72780850 polymorphism.Our results highlight the involvement of regulatory genetic variants of DDX1 in NB.
基金Supported by the Specialized Research Fund for the Doctoral Program of Higher Education,China (No. 200804230015)the National High Technology Research and Development Program of China (863 Program) (No. 2006AA10A401)
文摘RNA helicases of the DEAD-box and related families are involved in various cellular processes including DNA replication,DNA repair,and RNA processing.However,the function of DEAD-box proteins in aquaculture species is poorly understood at molecular level.We obtained the full-length cDNA sequences of two genes encoding helicase-related proteins,Fc-vasa and Fc-PL10a,from the testes of Chinese shrimp,Fenneropenaeus chinensis.The two predicted amino acid sequences contain all the conserved motifs characterized by the DEAD-box family and several RGG repeats in the N-terminal regions.Homology and phylogenetic analyses indicate that they belong to the vasa and PL10 subfamilies.The three-dimensional structures of the two proteins were predicted with a homology modeling approach.Both core proteins consist of two tandem RecA-like domains similar to those of the DEAD-box RNA helicase.Using reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR we found that Fc-vasa was expressed specifically in the adult gonads.Transcription decreased in the ovary but increased in the testis during gonadal development.Fc-PL10a expression was widely distributed in the tissues we examined.Using in situ hybridization,we demonstrated that the Fc-vasa transcript is localized to the cytoplasm of the spermatogonia and oocytes.Thus,our results suggest that Fc-vasa plays an important role in germ-line development,and has utility as a germ cell lineage marker which will help to generate new insight into the origin and differentiation of germ cells as well as the regulation of reproduction in F.chinensis.
基金Supported by Grants from the Ministry of Education of Singapore,Academic Research Fund Tier 1 Grant R-182-000-170-112
文摘The current therapeutic regimen to combat chronic hepatitis C is not optimal due to substantial side effects and the failure of a significant proportion of patients to achieve a sustained virological response.Recently developed direct-acting antivirals targeting hepatitis C virus(HCV)enzymes reportedly increase the virologic response to therapy but may lead to a selection of drug-resistant variants.Besides directacting antivirals,another promising class of HCV drugs in development include host targeting agents that are responsible for interfering with the host factors crucia for the viral life cycle.A family of host proteins known as DEAD-box RNA helicases,characterized by nine conserved motifs,is known to play an important role in RNA metabolism.Several members of this family such as DDX3,DDX5 and DDX6 have been shown to play a role in HCV replication and this review will summarize our current knowledge on their interaction with HCV.As chronic hepatitis C is one of the leading causes of hepatocellular carcinoma,the involvement of DEADbox RNA helicases in the development of HCC will also be highlighted.Continuing research on the interaction of host DEAD-box proteins with HCV and the contribution to viral replication and pathogenesis could be the panacea for the development of novel therapeutics against HCV.
